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It sounds like an oxymoron but low-fat yogurt may be more fattening than you think—at least for some people under some conditions. That is just one of the counterintuitive ideas behind new research to study the effects of a physiological condition known as insulin resistance in driving weight gain and obesity. Depending on what investigators find, some pretty conventional beliefs about what ultimately is fueling the current global epidemic of obesity—calories or carbohydrates—may need a bit of readjusting.

The scientific project is the brainchild of journalist Gary Taubes and former surgeon Peter Attia. Together they have founded a nonprofit organization called the Nutrition Science Initiative (NuSI), which has raised $40 million to test their hypothesis in the most rigorous manner possible. In essence, they contend that easily digested carbohydrates—such as the sugars that are added to low-fat yogurt to replace the fat that has been removed—drive weight gain by promoting insulin resistance. This hormonal change, in turn, signals the body to convert more sugar into fat and to hold on to more of the fat found in food rather than just letting these ingredients be excreted in the stool or converted into something else—like cholesterol or heat.

Independent investigators will monitor a number of overweight and obese volunteers who are fed various combinations of low-fat or low-carb diets for the effects on their bodies. In order to leave as little as possible to chance, the volunteers will have to live at a research facility during the experiment.

Taubes expects that NuSi may have preliminary results sometime within the next year or so. He has outlined the details of his new experiment in the September issue of Scientific American. Taubes also appears in an hour-long video from 2012 (see below) in which he debates the general concepts with Christopher Gardner, a nutrition professor at Stanford Medical School.